veverimer (TRC101) / Tricida - LARVOL DELTA

Veverimer, a Non-Absorbed Gastrointestinal Tract HCl Binder, Decreases Renal Ammoniagenesis and Mitigates Nephrotoxic Serum Nephritis. (PubMed, Kidney360) - "Veverimer-mediated bicarbonate generation can suppress renal ammoniagenesis and complement activation. These findings suggest a potential benefit of veverimer/ bicarbonate therapy in selected complement-mediated renal diseases."

Journal • Gastrointestinal Disorder • Nephrology • Renal Disease • EDN1 • IL6 • PTPRC • TGFB1

Among Patients Meeting the KDIGO CKD Practice Point Criterion for Treatment of Metabolic Acidosis, Higher Serum Bicarbonate Concentrations Are Associated with Slower CKD Progression (KIDNEY WEEK 2024) - "We explored the relation between achieved serum bicarbonate and CKD progression using data from the VALOR-CKD study, which evaluated the safety and efficacy of veverimer, a non-absorbed polymer that removes hydrochloric acid from the gastrointestinal tract.In this study, 1,480 patients with CKD (eGFR 20-40 mL/min/1.73 m2) and metabolic acidosis (serum bicarbonate 12-20 mEq/L) were randomized, after a single-blind active treatment period, to veverimer or placebo and followed for a median of 24.5 months. This post-hoc analysis from the VALOR-CKD trial provides supportive evidence that in a CKD population with serum bicarbonate concentrations meeting the KDIGO practice point criterion for treatment of metabolic acidosis (< 18 mEq/L), higher achieved serum bicarbonate concentrations are associated with slower CKD progression."

Clinical • Chronic Kidney Disease • Gastrointestinal Disorder • Metabolic Disorders

Serum Bicarbonate Concentrations and CKD Progression in Patients with Metabolic Acidosis: Evidence from VALOR-CKD (NKF-SCM 2024) - "This post-hoc analysis from the VALOR-CKD trial provides supportive evidence that higher serum bicarbonate concentrations in patients with CKD and metabolic acidosis are associated with slower CKD progression."

Clinical • Chronic Kidney Disease • Gastrointestinal Disorder • Metabolic Disorders • Nephrology • Transplantation

A basic solution for a complex problem: does treatment of metabolic acidosis slow CKD progression? (PubMed, Curr Opin Nephrol Hypertens) - "The current body of literature does not support the routine treatment of metabolic acidosis in patients with CKD and the authors agree with the forthcoming KDIGO guidelines to de-emphasize this common practice."

Journal • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of Chronic Kidney Disease in Patients with Metabolic Acidosis. (PubMed, J Am Soc Nephrol) - "Among patients with CKD and metabolic acidosis, treatment with veverimer did not slow CKD progression. The lower than expected bicarbonate separation may have hindered the ability to test the hypothesis. (Funded by Tricida, Inc.; VALOR-CKD ClinicalTrials.gov number, NCT037102)."

Clinical • Journal • Chronic Kidney Disease • Gastrointestinal Disorder • Metabolic Disorders • Nephrology • Renal Disease • Transplantation

Effects of correcting metabolic acidosis on muscle mass and functionality in chronic kidney disease: a systematic review and meta-analysis. (PubMed, J Cachexia Sarcopenia Muscle) - "Eleven studies performed an intervention with oral sodium bicarbonate compared with either placebo or with standard care and one study compared veverimer, an oral HCl-binding polymer, with placebo...Correcting metabolic acidosis in patients with CKD improves muscle mass and physical function. Correction of metabolic acidosis should be considered as part of the nutritional care for patients with CKD."

Journal • Retrospective data • Review • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

"From the veverimer study" (@shivadas29)

Metabolic Acidosis in Chronic Kidney Disease: An Update (KSN 2023) - "A recent study showed that veverimer was effective in treating metabolic acidosis in women with CKD, and significantly improved how they felt and functioned. A large-scale RCT is ongoing to evaluate the effectiveness of veverimer in slowing the progression of CKD."

Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

Sodium zirconium cyclosilicate and metabolic acidosis: Potential mechanisms and clinical consequences. (PubMed, Biomed Pharmacother) - "Mechanistically, these findings are consistent with SZC binding the ammonium ion (NH) generated from urea by gut microbial urease, preventing its absorption and, thus, preventing the liver regeneration of urea and promoting the fecal excretion of H. This mechanism of action may potentially result in benefits dependent on corrected metabolic acidosis (e.g., improved well-being, decreased catabolism, improved CKD mineral bone disorder, better control of serum phosphate, slower progression of CKD) and dependent on lower urea levels, such as decreased protein carbamylation. A roadmap is provided to guide research into the mechanisms and clinical consequences of the impact of SZC on serum bicarbonate and urate."

Journal • Review • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Orthopedics • Renal Disease

VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of CKD in Patients With Metabolic Acidosis (KIDNEY WEEK 2022) - "Topline data and results for the VALOR-CKD trial will be available in October 2022. Conclusion VALOR-CKD will test the efficacy of veverimer to slow CKD progression and preserve physical function, along with safety, in patients with CKD and chronic metabolic acidosis."

Clinical • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Gastrointestinal Disorder • Heart Failure • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • Transplantation

Veverimer for Slowing the Progression of CKD: The VALOR-CKD Trial (KIDNEY WEEK 2022) - "WITHDRAWN"

Design and Population of the VALOR-CKD Study: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating the Efficacy and Safety of Veverimer in Slowing Progression of Chronic Kidney Disease in Patients with Metabolic Acidosis. (PubMed, Nephrol Dial Transplant) - "VALOR-CKD has recruited a large population of people with metabolic acidosis at high risk for CKD progression to determine the effects of veverimer on the risk of progressive loss of kidney function."

Clinical • Journal • Cardiovascular • Chronic Kidney Disease • Diabetes • Gastrointestinal Disorder • Hypertension • Metabolic Disorders • Nephrology • Renal Disease

"#KidneyWk #KIDNEYWEEK2022 disappointing negative results with Veverimer (acidosis medication)" (@ElfadawyN)

Metabolic Disorders

"Another nail in the bicarbonate supplementation story? Veverimer coming tomorrow from @NavTangri #KidneyWk #LBCT posters" (@hswapnil)

"Personally, particularly interested in veverimer, cool dialysate and cemdisiran" (@VelezNephHepato)

Management of Metabolic Acidosis in Chronic Kidney Disease: Past, Present, and Future Direction. (PubMed, Adv Chronic Kidney Dis) - "Additionally, veverimer, an investigational, nonabsorbed polymer that binds and removes gastrointestinal hydrochloric acid, is being developed as a novel treatment for MA. As further studies define how to best use these interventions for kidney protection, clinicians must become aware of their potential utility in the management of patients with CKD. The aim of the present review is to explore the various intervention strategies that increase or normalize serum [HCO] in patients with CKD-associated MA or low normal serum [HCO] that may further slow progression of CKD."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetes • Gastrointestinal Disorder • Hypertension • Metabolic Disorders • Nephrology • Renal Disease

VALOR-CKD: Evaluation of Effect of TRC101 on Progression of Chronic Kidney Disease in Subjects With Metabolic Acidosis (clinicaltrials.gov) - P3b | N=1480 | Terminated | Sponsor: Tricida, Inc. | Trial completion date: Dec 2024 ➔ Sep 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2024 ➔ Aug 2022; Administrative reasons

Trial completion date • Trial primary completion date • Trial termination • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

Veverimer and Mitochondrial Energetics in Persons With CKD (clinicaltrials.gov) - P2 | N=102 | Not yet recruiting | Sponsor: University of California, Davis | Initiation date: Dec 2021 ➔ Jul 2022

Trial initiation date • Chronic Kidney Disease • Diabetes • Fatigue • Metabolic Disorders • Nephrology • Renal Disease

Effects of veverimer on serum bicarbonate and physical function in women with chronic kidney disease and metabolic acidosis: a subgroup analysis from a randomised, controlled trial. (PubMed, BMC Nephrol) - P3 | "Veverimer was effective in treating metabolic acidosis in women with CKD, and significantly improved how they felt and functioned."

Journal • Chronic Kidney Disease • Gastrointestinal Disorder • Metabolic Disorders • Nephrology • Renal Disease

Diagnosing metabolic acidosis in chronic kidney disease: importance of blood pH and serum anion gap. (PubMed, Kidney Res Clin Pract) - "Furthermore, acidosis with a high anion gap has recently been recognized as an important prognostic factor, because veverimer, a nonabsorbable hydrochloride-binding polymer, has been shown to improve kidney function and decrease the anion gap...Recent analyses using marginal structural models showed that acidosis with a high anion gap was associated with a high risk of CKD. Based on these observations, reconsideration of the clinical approach to diagnosing and treating metabolic acidosis in CKD may be warranted."

Journal • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

VALOR-CKD: Evaluation of Effect of TRC101 on Progression of Chronic Kidney Disease in Subjects With Metabolic Acidosis (clinicaltrials.gov) - P3b; N=1600; Active, not recruiting; Sponsor: Tricida, Inc.; Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

Metabolic Acidosis in Chronic Kidney Disease: Pathogenesis, Clinical Consequences, and Treatment. (PubMed, Electrolyte Blood Press) - "Veverimer, a non-absorbed, counterion-free, polymeric drug, is emerging to treat metabolic acidosis, but further researches are awaited. Further studies are also needed to clarify the target therapeutic range of serum bicarbonate and the drugs used for metabolic acidosis."

Clinical • Journal • Review • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

Metabolic Acidosis in Patients with CKD: Epidemiology, Pathogenesis, and Treatment. (PubMed, Kidney Dis (Basel)) - "The role of the new drug veverimer in the metabolic acidosis therapy needs further studies. The aim of this review article is to summarize the current knowledge concerning the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients."

Clinical • Journal • Review • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

Safety and Efficacy of Veverimer in Acidotic Patients With CKD and Heart Failure. (PubMed, Kidney Int Rep) - No abstract available

Clinical • Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure

Effects of Veverimer in Older Adults With CKD and Metabolic Acidosis. (PubMed, Kidney Med) - No abstract available

Clinical • Journal • Metabolic Disorders